Pyrimidinone-1,3-oxathiolane derivatives with antiviral activity

Abstract

Compounds of formula (I) wherein Ra and Rb the same or different, are hydrogen atoms, acyl groups deriving from a lower carboxylic acid or chains of formula (a) useful as reverse transcriptase inhibitors antiviral activity are described.

What is claimed is:  
     
       1. A compound of formula                    
       wherein 
       R a  and R b  are the same or different and are selected from the group consisting of hydrogen, acyl group derived from a lower carboxylic acid or chains of the formula                    
       wherein 
       R is a group of formula                    
       wherein 
       R 3  is selected from the group consisting of hydrogen, halogen, trifluoromethyl and C 1 -C 3  alkoxy;  
       R 1  and R 2  are the same or different and are selected from the group consisting of hydrogen, phenylalkoxycarbonyl having 1 to 3 carbon atoms in the alkoxy moiety, C 2 -C 6  alkoxycarbonyl and C 2 -C 6  alkylcarbonyl;  
       W is selected from the group consisting of a single bond, an oxygen atom and a group —CH(Alk)—, wherein Alk is a linear or branched C 1 -C 3  alkyl group;  
       r is 0 or 1, wherein when r is 0, n is 1 to 6, and when r is 1, n is 2 to 7; and  
       m is 2 to 7,  
       provided that at least one of R a  and R b  is other than a hydrogen atom or an acyl group derived from a lower carboxylic acid.  
     
     
       2. A compound according to claim  1  of formula                    
       wherein R, R 1 , R 2 , W, n, m and r have the meanings reported in claim  1  and R′ b  is a hydrogen atom or an acyl group deriving from a lower carboxylic acid. 
     
     
       3. A compound according to claim  1  of formula                    
       wherein R, R 1 , R 2 , W, n, m and r have the meanings reported in claim  1  and R′ a  is a hydrogen atom or an acyl group deriving from a lower carboxylic acid. 
     
     
       4. A compound according to claim  1  of formula                    
       wherein R, R 1 , R 2 , W, n, m and r have the meanings reported in claim  1 . 
     
     
       5. A compound according to claim  1  having the (2R,5S) configuration of lamivudine. 
     
     
       6. A compound according to claim  1  wherein R 1  and R 2  are C 2 -C 6  alkoxycarbonyl groups. 
     
     
       7. A compound according to claim  6  wherein R 1  and R 2  are tert-butoxycarbonyl groups. 
     
     
       8. A compound according to claim  1  wherein W is a single bond and R 3  is a hydrogen atom or a trifluoromethyl group. 
     
     
       9. A compound according to claim  8  wherein n is 4 to 6 and m is 4 to 5. 
     
     
       10. A compound according to claim  1  wherein R 1  and R 2  are other than hydrogen. 
     
     
       11. A process for the preparation of the compounds according to claim  1  comprising the acylation of lamivudine                    
       by reaction with a compound of formula                    
       wherein R, R 1 , R 2 , n, m and W have the meanings reported in claim  1  and R 4  is an OH group or a suitable leaving group when W is different from oxygen or R 4  is a suitable leaving group when W is oxygen. 
     
     
       12. A pharmaceutical composition containing one or more compounds according to claim  1  in admixture with a pharmaceutically acceptable carrier.